Different Doses of Sirolimus for the Maintenance Treatment of Kaposiform Hemangioendothelioma

NCT05324384 | Unknown Phase 2 DMC

• 1 other identifier: 2022-405
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to compare the efficacy and safety of different doses of sirolimus in the maintenance treatment of kaposiform hemangioendothelioma.

Conditions

Hemangioendothelioma

Keywords

Kaposiform hemangioendothelioma; Hemangioendothelioma; Sirolimus

Outcome Measures

Primary Outcomes (1)

• The changes in KHE volume

  Response to therapy was measured by volumetric magnetic resonance imaging (MRI) analyses were performed at baseline and 6 and 12 months after treatment and were independently assessed by 2 radiologists. Changes in KHE size were classified as further growth (increase of ≥10%), no change (\<10% increase and \<10% decrease), partial involution (decrease of ≥10% and \<75%), nearly complete involution (decrease of ≥75% and \<100%), or complete involution (100%).

  12 months.

Secondary Outcomes (6)

• Quality of life (QOL) in patients

  Baseline, 6 months, 12 months.

• Frequency of adverse events

  Baseline, 6 months, 12 months.

• The changes in the patient's musculoskeletal complication.

  Baseline, 3 monthss, 6 months, 9 months, 12 months.

• The changes of platelet counts.

  Baseline, 3 monthss, 6 months, 9 months, 12 months.

• The changes of fibrinogen levels.

  Baseline, 3 monthss, 6 months, 9 months, 12 months.

Study Arms (2)

Low dose of sirolimus

EXPERIMENTAL

The plasma trough concentration of sirolimus is maintained within the range of 10-15 ng/ml by adjusting sirolimus dose, for 6 months. Then, The plasma trough concentration of sirolimus is maintained within the range of 5-8 ng/ml by adjusting sirolimus dose, for 6 months.

Drug: Sirolimus

Regular dose of sirolimus

ACTIVE COMPARATOR

Sirolimus The plasma trough concentration of sirolimus is maintained within the range of 10-15 ng/ml by adjusting sirolimus dose, for 1 year.

Drug: Sirolimus

Interventions

Sirolimus DRUG

Use of different doses of the same drug

Also known as: Rapamycin, Rapamune

Low dose of sirolimus; Regular dose of sirolimus

Eligibility Criteria

• Age: Up to 14 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Presenting a KHE with the following characteristics:
• Male and female;
• Between 0 and 14 years of age;
• Diagnosis of KHE as determined by:
• Biopsy;
• Compatible MRI findings;
• History and clinical features.
• Patients were required to have adequate liver, renal and bone marrow function, and absence of active infection
• Consent of parents (or the person with parental authority in families): signed and dated written informed consent.

You may not qualify if:

• Patients contraindicated for the administration of sirolimus (e.g., those with an allergy to sirolimus or other rapamycin analog)
• Exposure to chemotherapy, embolization, corticosteroids, propranolol, sclerotherapy or any other investigational agents within 1 weeks before enrolment on study;
• Patients had a history of a major surgery within 2 weeks before enrollment;
• Patients who have a history of treatment with sirolimus or other mTOR inhibitor;
• Any known evidence of significant local or systemic uncontrolled infection, defined as receiving intravenous antibiotics at the time of enrollment;
• Concurrent severe and/or uncontrolled medical diseases that could compromise participation in the study (e.g. uncontrolled diabetes, uncontrolled hypertension, severe malnutrition, chronic liver or renal disease, active upper gastrointestinal tract ulceration).
• Impairment of gastrointestinal function or chronic gastrointestinal disease that may significantly alter the absorption of sirolimus.
• Patients with inadequate liver function:
• Total bilirubin higher than or equal to 1.5 × the upper limit of the normal (ULN) for age and alanine aminotransferase and aspartate aminotransferase higher than or equal to 2.5 × the ULN for age.
• Patients with inadequate renal function:
• years of age maximum serum creatinine (mg/dL) of 0.8; 6-10 years of age maximum serum creatinine (mg/dL) of 1.0; 11-14 years of age maximum serum creatinine (mg/dL) of 1.2;
• Adequate bone marrow function:
• Absolute neutrophil count lower than 1 × 109/L;
• History of a malignancy within 5 years;
• HIV infection or known immunodeficiency;

Sponsors & Collaborators

• West China Hospital: lead

Study Sites (1)

West China Hospital of Sichuan University

Chengdu, Sichuan, 610041, China

RECRUITING

Related Publications (6)

• Ji Y, Chen S, Yang K, Xia C, Li L. Kaposiform hemangioendothelioma: current knowledge and future perspectives. Orphanet J Rare Dis. 2020 Feb 3;15(1):39. doi: 10.1186/s13023-020-1320-1.

  PMID: 32014025 RESULT

• Wang Z, Yao W, Sun H, Dong K, Ma Y, Chen L, Zheng S, Li K. Sirolimus therapy for kaposiform hemangioendothelioma with long-term follow-up. J Dermatol. 2019 Nov;46(11):956-961. doi: 10.1111/1346-8138.15076. Epub 2019 Sep 5.

  PMID: 31489702 RESULT

• Ji Y, Chen S, Xiang B, Li K, Xu Z, Yao W, Lu G, Liu X, Xia C, Wang Q, Li Y, Wang C, Yang K, Yang G, Tang X, Xu T, Wu H. Sirolimus for the treatment of progressive kaposiform hemangioendothelioma: A multicenter retrospective study. Int J Cancer. 2017 Aug 15;141(4):848-855. doi: 10.1002/ijc.30775. Epub 2017 May 26.

  PMID: 28486787 RESULT

• Croteau SE, Liang MG, Kozakewich HP, Alomari AI, Fishman SJ, Mulliken JB, Trenor CC 3rd. Kaposiform hemangioendothelioma: atypical features and risks of Kasabach-Merritt phenomenon in 107 referrals. J Pediatr. 2013 Jan;162(1):142-7. doi: 10.1016/j.jpeds.2012.06.044. Epub 2012 Aug 4.

  PMID: 22871490 RESULT

• Rossler J, Baselga E, Davila V, Celis V, Diociaiuti A, El Hachem M, Mestre S, Haeberli D, Prokop A, Hanke C, Loichinger W, Quere I, Baumgartner I, Niemeyer CM, Kapp FG. Severe adverse events during sirolimus "off-label" therapy for vascular anomalies. Pediatr Blood Cancer. 2021 Aug;68(8):e28936. doi: 10.1002/pbc.28936. Epub 2021 Feb 13.

  PMID: 33580918 RESULT

• Ji Y, Chen S, Zhou J, Yang K, Zhang X, Xiang B, Qiu T, Gong X, Zhang Z, Lan Y, Hu F, Kong F, Qiu Q, Zhang Y. Sirolimus plus prednisolone vs sirolimus monotherapy for kaposiform hemangioendothelioma: a randomized clinical trial. Blood. 2022 Mar 17;139(11):1619-1630. doi: 10.1182/blood.2021014027.

  PMID: 35030255 RESULT

MeSH Terms

Conditions

Hemangioendothelioma; Kaposiform Hemangioendothelioma

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Hemangioma; Neoplasms, Vascular Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Yi Ji, MD, PhD

  West China Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yi Ji, MD, PhD

CONTACT

86 28 85423453; jijiyuanyuan@163.com

Siyuan Chen, MD, PhD

CONTACT

86 28 85422215; siy_chen@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 5, 2022
• First Posted: April 12, 2022
• Study Start: April 5, 2022
• Primary Completion: April 30, 2025
• Study Completion: November 30, 2025
• Last Updated: January 24, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)